| Full description or abstract |
Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We detected homozygous nonsense and frameshift mutations in LCA5 in five families affected with LCA. In a sixth family, the LCA5 transcript was completely absent. LCA5 is expressed widely throughout development, although the phenotype in affected individuals is limited to the eye. Lebercilin localizes to the connecting cilia of photoreceptors and to the microtubules, centrioles and primary cilia of cultured mammalian cells. Using tandem affinity purification, we identified 24 proteins that link lebercilin to centrosomal and ciliary functions. Members of this interactome represent candidate genes for LCA and other ciliopathies. Our findings emphasize the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA. |
| Source publication |
Pubmed 17546029 Authors: den Hollander AI,Koenekoop RK,Mohamed MD,Arts HH,Boldt K,Towns KV,Sedmak T,Beer M,Nagel-Wolfrum K,McKibbin M,Dharmaraj S,Lopez I,Ivings L,Williams GA,Springell K,Woods CG,Jafri H,Rashid Y,Strom TM,van der Zwaag B,Gosens I,Kersten FF,van Wijk E,Veltman JA,Zonneveld MN,van Beersum SE,Maumenee IH,Wolfrum U,Cheetham ME,Ueffing M,Cremers FP,Inglehearn CF,Roepman R |
